Clonally related follicular lymphomas and histiocytic/dendritic cell sarcomas: evidence for transdifferentiation of the follicular lymphoma clone

• Published in: Blood 2008-06, Vol.111 (12), p.5433-5439
• Main Authors: Feldman, Andrew L., Arber, Daniel A., Pittaluga, Stefania, Martinez, Antonio, Burke, Jerome S., Raffeld, Mark, Camos, Mireia, Warnke, Roger, Jaffe, Elaine S.
• Format: Article
• Language: English
• Subjects: Adult; Aged; Cell Differentiation; Cell Lineage; Cell Transdifferentiation; Dendritic Cell Sarcoma, Follicular - genetics; Dendritic Cell Sarcoma, Follicular - pathology; Dendritic Cells, Follicular - pathology; Dendritic Cells, Follicular - physiology; Female; Gene Expression Regulation, Neoplastic; Gene Rearrangement; Histiocytic Sarcoma - genetics; Histiocytic Sarcoma - pathology; Humans; Immunohistochemistry; Immunophenotyping; In Situ Hybridization, Fluorescence; Lymphoma, Follicular - genetics; Lymphoma, Follicular - pathology; Male; Middle Aged; Neoplasms, Second Primary - genetics; Neoplasms, Second Primary - pathology; Plenary Paper; Polymerase Chain Reaction
• ISSN: 0006-4971; 1528-0020
• DOI: 10.1182/blood-2007-11-124792

Rare cases of histiocytic and dendritic cell (H/DC) neoplasms have been reported in patients with follicular lymphoma (FL), but the biologic relationship between the 2 neoplasms is unknown. We studied 8 patients with both FL and H/DC neoplasms using immunohistochemistry, fluorescence in situ hybridization (FISH) for t(14;18), and polymerase chain reaction (PCR)/sequencing of BCL2 and IGH rearrangements. There were 5 men and 3 women (median age, 59 years). All cases of FL were positive for t(14;18). The H/DC tumors included 7 histiocytic sarcomas, 5 of which showed evidence of dendritic differentiation, and 1 interdigitating cell sarcoma. Five H/DC tumors were metachronous, following FL by 2 months to 12 years; tumors were synchronous in 3. All 8 H/DC tumors showed presence of the t(14;18) either by FISH, or in 2 cases by PCR with the major breakpoint region (MBR) probe. PCR and sequencing identified identical IGH gene rearrangements or BCL2 gene breakpoints in all patients tested. All H/DC tumors lacked PAX5, and up-regulation of CEBPβ and PU.1 was seen in all cases tested. These results provide evidence for a common clonal origin of FL and H/DC neoplasms when occurring in the same patient, and suggest that lineage plasticity may occur in mature lymphoid neoplasms.